Continuous In‐Line Virus Inactivation for Next Generation Bioprocessing

Abstract

Viral inactivation plays a critical role in assuring the safety of monoclonal antibody (mAb) therapeutics. Traditional viral inactivation involves large holding tanks in which product is maintained at a target low pH for a defined hold time, typically 30-60 min. The drive toward continuous processing and improved facility utilization has provided motivation for development of a continuous viral inactivation process. To this end, a lab-scale prototype viral inactivation system was designed, built, and characterized. Multiple incubation chamber designs are evaluated to identify the optimal design that enables narrow residence time distributions in continuous flow systems. Extensive analysis is conducted supporting rapid low pH viral inactivation and included evaluations with multiple viruses, a range of pH levels, buffer compositions, mAb concentrations, and temperatures. Multiple test conditions are evaluated using the in-line system and results compared to traditional batch-mode viral inactivation. Comparability in kinetics of virus inactivation suggests equivalency between the two approaches.

Truly continuous low pH viral inactivation for biopharmaceutical process integration

“…Typically these include, at least, pH‐value, temperature, and minimum incubation time (Brorson et al, 2003; Mattila et al, 2016). Protein concentration and buffer salt might also impact the logarithmic reduction values (LRVs; Gillespie et al, 2018; Kreil & Roush, 2018). Temperature and pH‐value can be easily controlled through thermostats and in‐line mixers, respectively.…”

Continuous Solvent/Detergent Virus Inactivation Using a Packed‐Bed Reactor

“…The curvature and direction changes induce a secondary flow pattern and momentum shifts, which contribute to narrower RTD. Segregation of fluid parcels inside a tubular reactor, either by immiscible fluid or mechanically, has also been proposed but execution at scale would be challenging . The RTD for any given reactor can be assessed by a pulse of non‐interacting tracer and calculation of the F ‐curve, the cumulative RTD function .…”

Integrated Continuous Biomanufacturing: Industrialization on the Horizon

“…On the downstream front, Pall Biotech explore the productivities and cost savings with continuous chromatography setups. There are also two contributions providing insights on continuous virus inactivation from Boehringer Ingelheim and MilliporeSigma with an additional Commentary from BOKU (Austria) …”